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Meningiomas exhibit loss of heterozygosity of the APC gene

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Abstract

The molecular mechanisms and candidate genes involved in development of meningiomas still need investigation and elucidation. In the present study 33 meningiomas were analyzed regarding genetic changes of tumor suppressor gene Adenomatous polyposis coli (APC), a component of the wnt signaling. Gene instability was tested by polymerase chain reaction/loss of heterozygosity (LOH) using Restriction Fragment Length Polymorphism (RFLP) method. RFLP was performed by two genetic markers, Rsa I in APC’s exon 11 and Msp I in its exon 15. The results of our analysis showed altogether 15 samples with LOH of the APC gene out of 32 heterozygous patients (47%). Seven patients had LOHs at both exons, while four LOHs were exclusive for exon 11 and four for exon 15. The changes were distributed according to pathohistological grade as follows: 46% of meningothelial meningioma showed LOH; 33% of fibrous; 75% of mixed (transitional); 75% of angiomatous, and one LOH was found in a single case of psammomatous meningioma. None of the LOHs were found in atypical and anaplastic cases. Immunostaining showed that samples with LOHs were accompanied with the absence of APC protein expression or presence of mutant APC proteins (χ2 = 13.81, df = 2, P < 0.001). We also showed that nuclear localization of β-catenin correlates to APC genetic changes (χ2 = 21.96, df = 2, P < 0.0001). The results of this investigation suggest that genetic changes of APC gene play a role in meningioma formation.

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Acknowledgments

This work was supported by grant 108-1081870–1905 from Ministry of Science Sports and Education, Republic of Croatia.

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Authors and Affiliations

  1. Laboratory of Neurooncology, Croatian Institute for Brain Research, Medical School University of Zagreb, Šalata 12, 10000, Zagreb, Croatia

    Nives Pećina-Šlaus, Tamara Nikuševa Martić & Martina Zeljko

  2. Department of Biology, Medical School University of Zagreb, Šalata 3, 10000, Zagreb, Croatia

    Nives Pećina-Šlaus & Tamara Nikuševa Martić

  3. Ljudevit Jurak Department of Pathology, University Hospital “Sisters of Charity”, Vinogradska 29, 10000, Zagreb, Croatia

    Davor Tomas & Hrvoje Čupić

  4. Department of Neurosurgery, University Hospital “Sisters of Charity”, Vinogradska 29, 10000, Zagreb, Croatia

    Vili Beroš

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  1. Nives Pećina-Šlaus
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  2. Tamara Nikuševa Martić
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Correspondence to Nives Pećina-Šlaus.

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Pećina-Šlaus, N., Nikuševa Martić, T., Tomas, D. et al. Meningiomas exhibit loss of heterozygosity of the APC gene. J Neurooncol 87, 63–70 (2008). https://doi.org/10.1007/s11060-007-9500-6

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  • DOI: https://doi.org/10.1007/s11060-007-9500-6

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